Background Treatment with tumor necrosis factor inhibitors (TNFi) such as etanercept (ETN) is effective in patients with rheumatoid arthritis (RA). However, not all patients respond to treatment. Physicians would be able to better provide the best treatment to their patients if there were criteria that identified potential good responders to TNFi therapy.
Objectives To evaluate criteria at baseline for their predictive value for (1) initial response to ETN treatment at week 24, and (2) for maintaining low disease activity (LDA) or remission at week 52 using data from the T2T trial (NCT01981473).
Methods Patients with moderate-to-severe RA were treated with 50 mg ETN (ETN50) on a background of methotrexate ± disease-modifying anti-rheumatic drugs (DMARDs) for 24 weeks (open-label, Period 1 (P1)). Patients achieving LDA (Disease Activity Score-28 joints (DAS28)–erythrocyte sedimentation rate (ESR)<3.2) at week 24 were randomized to continue ETN50 or switched to placebo (PBO) for another 28 weeks (Period 2 (P2)). Baseline variables were analyzed for the probability of patients achieving DAS28-ESR or Clinical Disease Activity Index (CDAI) LDA (<3.2) at the end of P1 and to determine whether patients in remission maintained it at the end of P2. All data were evaluated using logistic regression analysis.
Results Evaluable data were available for 473 of the 491 patients enrolled in P1. After 24 weeks of ETN treatment (end of P1), only being female (p=0.031) and using DMARDs (p=0.029) were predictive of patients being able to achieve DAS28-ESR LDA (<3.2). Younger patients and patients with lower DAS28-ESR, ESR, and Health Assessment Questionnaire–Disability Index (HAQ-DI) showed a statistically significant greater probability to achieve remission (DAS28-ESR<2.6) at the end of P1. Patients with lower DAS28-ESR, DAS28-C-reactive protein (CRP), CDAI, Simplified Disease Activity Index (SDAI), HAQ-DI, and shorter time to LDA in P1 at week 24 prior to entering P2 showed a statistically significant greater probability to maintain DAS28-ESR LDA or remission at week 52 for both patients who continued on ETN or were switched to PBO during P2. Younger patients (p=0.006) and patients with shorter disease duration (p=0.008) showed a statistically greater probability to achieve CDAI remission at week 24. Lower DAS28-ESR, DAS28-CRP, CDAI, SDAI, HAQ-DI, and shorter time to LDA in P1 at week 24 prior to entering P2 showed a statistically significant greater probability to maintain CDAI LDA or remission at week 52 for both patients who continued on ETN or were switched to PBO during P2. The proportion of patients who maintained LDA or remission was consistently greater in the ETN arm compared with the PBO arm. None of the other baseline variables were predictive of patients being able to achieve LDA or remission.
Conclusions In this post-hoc analysis, younger patients and patients with lower disease activity at baseline or shorter time to achieve LDA were more likely to achieve and maintain LDA or remission.
Acknowledgement Medical writing support was provided by Mukund Nori, PhD, MBA, CMPP, of Engage Scientific Solutions and funded by Pfizer.
Disclosure of Interest N. Akkoc Grant/research support from: Pfizer, UCB, MSD, Speakers bureau: Pfizer, AbbVie, MSD, UCB, C. A. Zerbini Grant/research support from: Pfizer, Consultant for: Pfizer, D. Karateev Grant/research support from: Pfizer, BMS, Consultant for: AbbVie, BMS, Celltrion, MSD, Pfizer, Speakers bureau: AbbVie, BMS, Medac, MSD, Pfizer, UCB, R. Pedersen Shareholder of: Pfizer, Employee of: Pfizer, B. Vlahos Shareholder of: Pfizer, Employee of: Pfizer, L. Marshall Shareholder of: Pfizer, Employee of: Pfizer, C. Bao: None declared, M. Al-Maini: None declared, Q. Shen Shareholder of: Pfizer, Employee of: Pfizer